Advanced dementia is a common, morbid and costly condition. Infectious and febrile episodes are hallmarks of end-stage dementia, and antimicrobials are extensively prescribed to patients dying with this condition. However, it remains unclear as to whether antimicrobial treatment confers any life-prolonging or symptomatic benefit in these terminally ill individuals, for whom the goal of care is often palliation. Moreover, prior work suggests that nursing home (NH) residents with advanced dementia may be reservoirs for antimicrobial resistant bacteria (ARB) in this setting. Antimicrobial use is a main factor leading to the emergence of ARB;a critical and rapidly growing public health problem. NH residents also contribute to the influx of ARB into the hospital setting. Taken together, the widespread antimicrobial use in advanced dementia raises serious concerns not only from the perspective of individual benefits and burdens near the end-of-life, but also from a public health standpoint with respect to the emergence and spread of antimicrobial resistance. The extent to which antimicrobials are inappropriately prescribed to NH residents with advanced dementia has never been examined. Thus, the over-riding goals of the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia (SPREAD) are to examine antimicrobial exposure in advanced dementia and further our understanding as to how that exposure contributes to the mergence of ARB. By conducting a prospective study of 400 NH residents with advanced dementia and their health care proxies, followed on a quarterly basis for up to 12 months, the specific aims are: 1. to describe the occurrence and management of infectious and febrile episodes, and identify potentially inappropriate antimicrobial initiation, 2. to assess decision-making for the management of infectious episodes, and identify modifiable aspects of care associated with higher quality decision-making, and 3. to characterize the baseline prevalence and dynamics (acquisition, loss, or persistence) of ARB colonization, and examine the association between antimicrobial exposure with ARB acquisition. IMPLICATIONS: The proposed work will promote our understanding of antimicrobial use in NH residents with advanced dementia, and its contribution to the emergence ARB. Aims 1 and 2 will identify modifiable factors contributing to excessive and possibly inappropriate use related to: 1. antimicrobial initiation, and 2. decision-making. Aim 3 will examine how this exposure contributes to ARB acquisition. If a substantial proportion of antimicrobial exposure is inappropriate, both in terms of meeting accepted standards for initiation and shared decision-making, these findings will lead to strategies aimed at optimizing antimicrobial use, and reducing ARB in these residents. In this way, improving the management of infections in advanced dementia has the potential to make important clinical and policy-relevant contributions by promoting high quality end-of- life care for the millions of Americans dying with this condition, and by addressing a rapidly growing public health threat in the NH setting. PUBLIC HEALTH RELEVANCE: The proposed work will promote our understanding of antimicrobial exposure in nursing home residents with advanced dementia, and its contribution to the emergence of antimicrobial resistance bacteria, a serious public health issue in the US. Improving the management of infections in advanced dementia has the potential to make important clinical and policy-relevant contributions by promoting high quality end-of-life care for the millions of American dying with this condition, and reducing a rapidly growing public health threat in the nursing home setting.